Cryoablation combined with zoledronic acid in comparison with ...

EXPERIMENTAL AND THERAPEUTIC MEDICINE 8: 539-544, 2014

Cryoablation combined with zoledronic acid in comparison with cryoablation and zoledronic acid alone in the treatment of painful bone metastases FENQIANG LI, WENHUI WANG, LI LI, DONGJUN SU, YAOWEN CHANG, GANG GUO, XUEWEN HE and BAOHUA LI Department of Interventional Medicine, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China Received December 21, 2013; Accepted May 8, 2014 DOI: 10.3892/etm.2014.1784 Abstract. This study aimed to examine the efficacy and safety of cryoablation, combined with zoledronic acid or alone, in the treatment of bone metastatic pain. A total of 84 patients were randomly divided into three groups: group  A (cryoablation plus zoledronic acid), group  B (cryoablation) and group  C (zoledronic acid). In group  A, the overall response [OR  = complete response (CR) + partial response (PR)] was 85.7% (24/28), the CR was 35.7% (10/28) and the PR was 50.0% (14/28). In group  B, the OR was 50.0% (14/28), the CR was 14.3% (4/28) and the PR was 35.7% (10/28). In group C, the OR was 67.9% (19/28), the CR was 21.4% (6/28) and the PR was 46.4% (13/28). The differences in OR, CR and PR among the three  groups were statistically significant (P15 min, for a total of >6 times. Group B patients were subject to targeted argon‑helium cryoablation to metastatic lesions once. Group C patients were monthly administered an injection of zoledronic acid (4  mg), as described for group A. Pretreatment patient assessment. Prior to therapy with cryoablation, the effect of focal painful bone metastasis was assessed by use of the verbal rating scale (VRS), and the KPS was used for assessment of the patient's quality of life. Analgesic medicine use was also recorded. Each patient was instructed to specifically respond to the VRS questions with respect to the focal painful metastasis that was to be treated. Patients were physically examined by an interventionalist prior to treatment to determine whether the site or sites of focal pain correlated with the available imaging, including CT, MRI and ultrasound imaging, which was obtained immediately following entrance

EXPERIMENTAL AND THERAPEUTIC MEDICINE 8: 539-544, 2014

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B

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C

Figure 1. Lung cancer with rib and vertebral metastasis and bone destruction, during the ablation procedure. CT scans showing (A) the insertion of cryoprobes into metastatic lesions and (B) the monitoring of the area of ablation, and (C) ensuring the ablation area completely covers the lesion. CT, computed tomography.

A

B

Figure 2. Breast cancer with lumbar vertebral metastasis. (A) The soft tissue tumor and lesion of the lumbar vertebral prior to the ablation procedure; (B) the ablation area completely covered the lesions.

A

B

Figure 3. Lung squamous carcinoma with rib metastasis. (A) Cryoprobes inserted into metastatic lesions under CT scan; (B) monitoring the area of ablation by CT scan. CT, computed tomography.

into the study. A complete blood count and prothrombin time were obtained within one week of the ablation procedure. Each patient's history of previous chemotherapy and radiation therapy was recorded. Complications were recorded throughout the follow‑up period and classified via Common Terminology Criteria for Adverse Events (CTCAE, version 4.03) (17). Cryoablation procedure. Following routine sterile preparation, 0.2% chloroprocaine was used to anesthetize the puncture point. The 1.7, 2.4 or 3.8 mm cryoprobes were placed into a 6, 9 or 11F sheath tube and inserted into the metastatic lesions; the feeding direction and depth were under the guidance of plain CT scanning. A single cryoprobe was placed for lesions ≤3 cm in diameter. For larger lesions, two to five

additional cryoprobes were systematically placed with CT guidance. Cryoablation treatments were focused on the margin of the lesion involving bone to treat the soft‑tissue‑bone interface (Fig. 1). Plain CT scanning was performed approximately every 2 min throughout the freezing portions of the cycle to monitor the growth of the ice ball (Fig. 2). Each lesion was subject to three freeze‑thaw‑freeze cycles, 20 min per cycle. Following each freezing cycle, the cryoprobes were warmed with active heating using helium gas until the temperature reached >20˚C. The cryoprobes were then withdrawn (Fig. 3). Test items. The pain improvement was continuously observed for 180 days following the treatments. One day prior to treatment and 7, 14 and 21 days following treatment, the general condition, blood calcium, blood routine, liver function, renal

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LI et al: CRYOABLATION COMBINED WITH ZOLEDRONIC ACID OR USED ALONE IN BONE METASTATIC PAIN

Table II. Analgesic evaluation of the three groups after 180 days. Group

n

CR, n (%)

PR, n (%)

NR, n (%)

CR+PR, n (%)

Z

P‑value

Group A 28 10 (35.7) Group B 28 4 (14.3) Group C 28 6 (21.4) 2 χ P‑value

14 (50.0) 10 (35.7) 13 (46.4) 22.699 0.000

4 (14.3) 14 (50.0) 9 (32.1)

24 (85.7) 14 (50.0) 19 (67.9)

4.729 3.116 3.887

0.000 0.032 0.002

CR, complete response; PR, partial response; NR, no response.

function, blood biochemistry, urine routine and electrocardiogram of patients were measured. The normal range of blood Ca2+ is 2.0‑2.6 mmol/l. Efficacy assessment criteria. The VRS was presented to the patient as a series of descriptions, ranked and numbered as follows: no pain, 0; mild pain, 1; moderate pain, 2; intense pain, 3; extremely intense pain, 4. The primary endpoints were complete response (CR) defined as the absence of pain without the need for increasing analgesic relief, and partial response (PR) defined as an improvement ≥2 on the ordinal scale with no requirement for increasing analgesic relief. The patients with the same or worse pain level at three weeks were considered to have no response (NR). The responses were assessed by follow‑up or with telephone interviews. The responses were examined at 3 and 24 weeks. The response durations were calculated from the first date evaluated at 3 weeks to the date of relapse, or in absence of relapse to the date of last assessment or mortality (18,19). Adverse reactions. Potential adverse reactions of the therapies include active bleeding, frostbite, fever, muscle pain, nausea and vomiting, skin rash, hypocalcemia and dysfunction of the kidneys and liver. Statistical analysis. Student's t‑test was used to assess the differences in age, KPS score and VRS score of each group. χ2 test was used to assess the differences in gender, malignant hypercalcemia, pain medication and primary tumor location and type. P